title: N-linked polylactosamine glycan synthesis is regulated by co-expression of β3GnT2 and GCNT2.
abstract: Poly-N-acetyllactosamine (PLN) is a unique glycan composed of repeating units of the common disaccharide (Galβ1,4-GlcNAcβ1,3)n . The expression of PLN on glycoprotein core structures minimally requires enzyme activities for β1,4-galactosyltransferase (β4GalT) and β1,3-N-acetylglucosminyltransferase (β3GnT). Because β4GalTs are ubiquitous in most cells, PLN expression is generally ascribed to the tissue-specific transcription of eight known β3GnT genes in mice. In the olfactory epithelium (OE), β3GnT2 regulates expression of extended PLN chains that are essential for axon guidance and neuronal survival. N-glycan branching and core composition, however, can also modulate the extent of PLN modification. Here, we show for the first time that the β1,6-branching glycosyltransferase GCNT2 (formerly known as IGnT) is expressed at high levels specifically in the OE and other sensory ganglia. Postnatally, GCNT2 is maintained in mature olfactory neurons that co-express β3GnT2 and PLN. This highly specific co-expression suggests that GCNT2 and β3GnT2 function cooperatively in PLN synthesis. In support of this, β3GnT2 and GCNT2 co-transfection in HEK293T cells results in high levels of PLN expression on the cell surface and on adenylyl cyclase 3, a major carrier of PLN glycans in the OE. These data clearly suggest that GCNT2 functions in vivo together with β3GnT2 to determine PLN levels in olfactory neurons by regulating β1,6-branches that promote PLN extension.
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Henion
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Schwarting
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D017349:N-Acetylhexosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000096:biosynthesis*; D011247:Pregnancy
chemical_list: D011134:Polysaccharides; C037199:poly-N-acetyllactosamine; C106501:N-acetylglucosaminyltransferase IGnT; C000617996:GCNT2 protein, human; D017351:N-Acetylglucosaminyltransferases; D017349:N-Acetylhexosaminyltransferases; C530032:B4gat1 protein, mouse